Abstract

Objective The National Cancer Center Network recommends starting radiation therapy within 6 weeks after surgery for oral cavity squamous cell carcinoma (OCSCC), but there is limited evidence of the importance of the total time from surgery to completion of radiation therapy (package time). We set out to determine if there was an association between package time and survival in OCSCC and to evaluate the impact of treatment location on outcomes. Study Design Retrospective cohort study. Setting Tertiary academic medical center. Subjects and Methods We reviewed the records of patients with OCSCC who completed postoperative radiation therapy at an academic medical center from 2008 to 2016. The primary endpoints were overall survival and recurrence-free survival. Statistical analysis included chi2 tests and Cox proportional hazards regressions. Results We identified 132 patients with an average package time of 12.6 weeks. On multivariate analysis, package time >11 weeks was independently associated with decreased overall survival (hazard ratio, 6.68; 95% CI, 1.42-31.44) and recurrence-free survival (hazard ratio, 2.94; 95% CI, 1.20-7.18). Patients who received radiation therapy at outside facilities were more likely to have treatment delays (90.2% vs 62.9%, P = .001). Conclusions Prolonged package times are associated with decreased overall and recurrence-free survival among patients with OCSCC. Patients who received radiation therapy at outside facilities are more likely to have prolonged package times.

Abstract

Objective The National Comprehensive Cancer Network guidelines recommend an interval between surgery and adjuvant radiation therapy of less than 6 weeks, but only 44% of patients meet this metric nationally. We sought to identify key components of an improvement process focused on starting adjuvant radiation therapy within 6 weeks of surgery. Methods This project used an A3 model to improve a defined process measure. We studied a consecutive sample of 56 patients with oral cavity carcinoma who were treated at our institution with upfront surgical resection followed by adjuvant radiation therapy. Twelve proposed interventions tested during the study period focused on 3 key drivers of delays: delayed dental evaluation and teeth extraction, delayed radiation oncology consults, and inadequate patient engagement. The primary outcome measure was the number of days from surgery to the start of radiation therapy. Results Prior to the intervention, 62% of patients received adjuvant radiation within 6 weeks of surgery. Following the intervention, 73% of patients achieved this metric. The percentage of patients with avoidable delays decreased from 24% to 9%. The percentage of patients with unavoidable delays was relatively constant before and after the intervention (15% and 18%, respectively). Discussion Defining disease-specific metrics is critical to improving care in our head and neck cancer patient population. We demonstrate several key components to develop and improve self-defined metrics. Implications for Practice As we transition to a system of value-based care, structured quality improvement projects can have a measurable impact on cancer patient process measures.

Abstract

Shortening the time from surgery to the start of radiation (TS-RT) is a consideration for physicians and patients. Although the National Comprehensive Cancer Network recommends radiation to start within 6 weeks, a survival benefit with this metric remains controversial.To determine the association of delayed TS-RT with overall survival (OS) using a large cancer registry.In this observational cohort study, 25216 patients with nonmetastatic stages III to IV head and neck cancer were identified from the National Cancer Database (NCDB).Patients received definitive surgery followed by adjuvant radiation therapy, with an interval duration defined as TS-RT.Overall survival as a function of TS-RT and the effect of clinicopathologic risk factors and accelerated fractionation.We identified 25216 patients with nonmetastatic squamous cell carcinoma of the head and neck. There were 18968 (75%) men and 6248 (25%) women and the mean (SD) age of the cohort was 59 (10.9) years. Of the 25216 patients, 9765 (39%) had a 42-days or less TS-RT and 4735 (19%) had a 43- to 49-day TS-RT. Median OS was 10.5 years (95% CI, 10.0-11.1 years) for patients with a 42-days or less TS-RT, 8.2 years (95% CI, 7.4-8.6 years; absolute difference, -2.4 years, 95% CI, -1.5 to -3.2 years) for patients with a 43- to 49-day TS-RT, and 6.5 years (95% CI, 6.1-6.8 years; absolute difference, -4.1 years, 95% CI, -3.4 to -4.7 years) for those with a 50-days or more TS-RT. Multivariable analysis found that compared with a 42-days or less TS-RT, there was not a significant increase in mortality with a 43- to 49-day TS-RT (HR, 0.98; 95% CI, 0.93-1.04), although there was for a TS-RT of 50 days or more (HR, 1.07; 95% CI, 1.02-1.12). A significant interaction was identified between TS-RT and disease site. Subgroup effect modeling found that a delayed TS-RT of 7 days resulted in significantly worse OS for patients with tonsil tumors (HR, 1.22; 95% CI, 1.05-1.43) though not other tumor subtypes. Accelerated fractionation of 5.2 fractions or more per week was associated with improved survival (HR, 0.93; 95% CI, 0.87-0.99) compared with standard fractionation.Delayed TS-RT of 50 days or more was associated with worse overall survival. The multidisciplinary care team should focus on shortening TS-RT to improve survival. Unavoidable delays may be an indication for accelerated fractionation or other dose intensification strategies.

Abstract

To describe the relationship between jaw opening and access to the deep parotid window, we identified the following distances in 10 human skulls: symphysis to angle of mandible, mastoid tip to angle of mandible, angle of mandible to condylar process, and mastoid tip to condylar process. With the jaw closed and open, these distances were measured with 1 to 3 wooden blocks, each measuring 1 cm, between the upper and lower incisors. The triangular deep parotid area formed by the last 3 distances was calculated. A repeated measures analysis of variance showed a significant decrease in the deep parotid area with increasing interincisal distance ( P < .01). A generalized estimating equation model demonstrated a statistically significant decreasing area of the deep parotid window with increasing interincisal distance. These results suggest that nasal intubation may improve access to the parotid window.

Abstract

Objectives Despite the epidemic of opioid overuse among American patients, there are limited data regarding the prevalence of such use among patients with head and neck cancer (HNC). Here, we report on the prevalence of persistent postoperative opioid (PPO) use and its risk factors among older patients with HNC undergoing surgery. Study Design Retrospective cohort study. Setting Surveillance, Epidemiology, and End Results (SEER)-Medicare linked cancer registry-claims database. Subjects and Methods We identified patients aged 66 years or older who were diagnosed with HNC from 2008 to 2013, underwent primary surgical resection for their cancers, and met certain insurance and discharge criteria. The primary outcome was PPO use, defined as new opioid prescriptions 90 to 180 days postoperatively. We used multivariable logistic regression to evaluate associations between PPO use and factors such as demographics and postoperative treatment. Results Of the 1190 eligible patients with HNC, 866 (72.8%) received opioid prescriptions attributable to their surgery. Among these 866 patients, the prevalence of PPO use was 33.3% overall; it was 48.3% among the 428 patients with preoperative opioid use compared to 18.5% among the 438 opioid-naive patients (adjusted odds ratio [OR], 3.96; 95% confidence interval [CI], 2.80-5.59). Other factors associated with PPO use include postoperative radiotherapy (OR, 1.99; 95%, CI 1.33-2.98) and Charlson comorbidity index (OR, 1.20; 95% CI, 1.03-1.41). Postoperative chemotherapy (OR, 1.19; 95% CI, 0.73-1.95) was not significantly associated with PPO use. Conclusions PPO use is a substantial problem in older surgical patients with HNC, one that warrants consideration of alternative treatment strategies and continued examination of prescription guidelines for patients with HNC.

Abstract

Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging. Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m2, cohort 2 received 25 mg/m2, and cohort 3 received 62.5 mg/m2. For panitumumab-IRDye800CW, cohorts received 0.06 mg/kg, 0.5 mg/kg, and 1 mg/kg, respectively. Electrocardiograms and blood samples were obtained, and patients were followed for 30 days post-study drug infusion. Results: Both fluorescently labeled antibodies had similar pharmacodynamic properties and minimal toxicities. Two infusion reactions occurred with cetuximab and none with panitumumab. There were no grade 2 or higher toxicities attributable to cetuximab-IRDye800CW or panitumumab-IRDye800CW; fifteen grade 1 adverse events occurred with cetuximab-IRDye800CW, and one grade 1 occurred with panitumumab-IRDye800CW. There were no significant differences in QTc prolongation between the two trials (p=0.8). Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other therapeutic antibodies may be repurposed as imaging agents with limited preclinical toxicology data.

Abstract

The utility of cancer databases for oropharyngeal cancer studies is limited by lack of information on human papillomavirus (HPV) status. The purpose of this study was to develop a surrogate that can be used to adjust for the effect of HPV status on survival.The study cohort included 6419 patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2012, identified in the National Cancer Database (NCDB). The HPV surrogate score was developed using a logistic regression model predicting HPV-positive status.The HPV surrogate score was predictive of HPV status (area under the curve [AUC] 0.73; accuracy of 70.4%). Similar to HPV-positive tumors, HPV surrogate positive tumors were associated with improved overall survival (OS; hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.59-0.91; P = .005), after adjusting for important covariates.The HPV surrogate score is useful for adjusting for the effect of HPV status on survival in studies utilizing cancer databases.

Abstract

Negative margins and lymph node yields (LNY) of 18 or more from neck dissections in patients with head and neck squamous cell carcinomas (HNSCC) have been associated with improved patient survival. It is unclear whether these metrics can be used to identify hospitals with improved outcomes.To determine whether 2 patient-level metrics would predict outcomes at the hospital level.A retrospective review of records from the National Cancer Database (NCDB) was used to identify patients who underwent primary surgery and concurrent neck dissection for HNSCC between 2004 and 2013. The percentage of patients at each hospital with negative margins on primary resection and an LNY 18 or more from a neck dissection was quantified. Cox proportional hazard models were used to define the association between hospital performance on these metrics and overall survival.Margin status and lymph node yield at hospital level. Overall survival (OS).We identified 1008 hospitals in the NCDB where 64738 patients met inclusion criteria. Of the 64738 participants, 45170 (69.8%) were men and 19568 (30.2%) were women. The mean SD age of included patients was 60.5 (12.0) years. Patients treated at hospitals attaining the combined metric of a 90% or higher negative margin rate and 80% or more of cases with LNYs of 18 or more experienced a significant reduction in mortality (hazard ratio [HR] 0.93; 95% CI, 0.89-0.98). This benefit in survival was independent of the patient-level improvement associated with negative margins (HR, 0.73; 95% CI, 0.71-0.76) and LNY of 18 or more (HR, 0.85; 95% CI, 0.83-0.88). Including these metrics in the model neutralized the association of traditional measures of hospital quality (volume and teaching status).Treatment at hospitals that attain a high rate of negative margins and LNY of 18 or more is associated with improved survival in patients undergoing surgery for HNSCC. These surgical outcome measures predicted outcomes independent of traditional, but generally nonmodifiable characteristics. Tracking of these metrics may help identify high-quality centers and provide guidance for institution-level quality improvement.

Abstract

The importance of providing quality care over quantity of care, and its positive effects on health care expenditure and health, has motivated a transition toward value-based payments. The Centers for Medicare and Medicaid Services and private payers are establishing programs linking financial incentives and penalties to adherence to quality measures. As payment models based on quality measures are transitioned into practice, it is beneficial to identify current quality measures that address breast reconstruction surgery as well as understand gaps to inform future quality measure development.We performed a systematic review of quality measures for breast reconstruction surgery by searching quality measure databases, professional society clinical practice guidelines, and the literature. Measures were categorized as structure, process, or outcome according to the Donabedian domains of quality.We identified a total of 27 measures applicable to breast reconstruction: 5 candidate quality measures specifically for breast reconstruction surgery and 22 quality measures that relate broadly to surgery. Of the breast reconstruction candidate measures, 3 addressed processes and 2 addressed outcomes. Seventeen of the general quality measures were process measures and 5 were outcome measures. We did not identify any structural measures.Currently, an overrepresentation of process measures exists, which addresses breast reconstruction surgery. There is a limited number of candidate measures that specifically address breast reconstruction. Quality measure development efforts on underrepresented domains, such as structure and outcome, and stewarding the measure development process for candidate quality measures can ensure breast reconstruction surgery is appropriately evaluated in value-based payment models.

Abstract

Multiple smaller studies have demonstrated an association between overall survival and lymph node (LN) count from neck dissection in patients with head and neck cancer. This is a large cohort study to examine these associations by using a national cancer database.The National Cancer Database was used to identify patients who underwent upfront nodal dissection for mucosal head and neck squamous cell carcinoma between 2004 and 2013. Patients were stratified by LN count into those with < 18 nodes and those with 18 nodes on the basis of prior work. A multivariable Cox proportional hazards regression model was constructed to predict hazard of mortality. Stratified models predicted hazard of mortality both for patients who were both node negative and node positive.There were 45,113 patients with 18 LNs and 18,865 patients with < 18 LNs examined. The < 18 LN group, compared with the 18 LN group, had more favorable tumor characteristics, with a lower proportion of T3 and T4 lesions (27.9% v 39.8%), fewer patients with positive nodes (46.6% v 60.5%), and lower rates of extracapsular extension (9.3% v 15.1%). Risk-adjusted Cox models predicting hazard of mortality by LN count showed an 18% increased hazard of death for patients with < 18 nodes examined (hazard ratio [HR] 1.18; 95% CI, 1.13 to 1.22). When stratified by clinical nodal stage, there was an increased hazard of death in both groups (node negative: HR, 1.24; 95% CI, 1.17 to 1.32; node positive: HR, 1.12; 95% CI, 1.05 to 1.19).The results of our study demonstrate a significant overall survival advantage in both patients who are clinically node negative and node positive when 18 LNs are examined after neck dissection, which suggests that LN count is a potential quality metric for neck dissection.

Abstract

Multiple disease processes, including neoplasia, trauma, and medication side-effects, necessitate segmental resection and subsequent reconstruction of the mandible. As surgical techniques have advanced, several technologies have been developed with the potential to significantly transform a surgeon's approach to the restoration of mandibular continuity. The purpose of this review is to highlight many of these relatively newer tools and discuss their evolving role in mandibular reconstruction.Several contemporary studies have documented the application of different approaches and modifications to mandibular reconstruction - including computer-aided design or computer-aided modeling, contemporary plating systems, osseointegrated implants, and various modifications to existing osseocutaneous free tissue transfer options - and have reported relatively high success rates.In discussing these reports, we present a survey of current and developing technologies in the field of mandibular reconstruction and aim to provide sufficient context for the gradual integration of these techniques into practice.

Abstract

Advanced head and neck cancer (HNC) is a complex group of diseases that requires the input and coordination of multiple providers. While there are general guidelines for treatment, there is also considerable variation in how patients are treated, and how long they survive after treatment. It is unclear how the treatment variations relate to treatment costs and survival.We identified 3678 Medicare patients with advanced HNC treated in 12 US regions between 2004 and 2009 using the linked database containing Medicare and Surveillance Epidemiology and End Results (SEER) data. We calculated average cost per patient during the period three months before to 12months after diagnosis for each region. Costs included inpatient hospital, outpatient, physician, and durable medical equipment charges. We also calculated three-year overall survival for each of the regions.The mean cost-per-patient varied substantially among the regions, ranging from $51,857 for Utah to $82,181 for Detroit. Utah incurred the lowest total costs within one year of advanced HNC diagnosis ($51,857 per patient, 95% CI $42,285-$61,429), whereas Detroit had the highest costs ($82,181 per patient, 95% CI $74,752-$89,610). Overall survival also varied among the regions, ranging from 45months in Kentucky to 58months in Washington. There was little correlation between expenditures and length of survival, with correlation coefficient of 0.0088.Despite significant variation in both expenditures and survival among the regions, we found no correlation between costs and mean survival time, suggesting that more costly care did not lead to improved outcomes.

Abstract

Prospective quality metrics for neck dissection have not been established for patients with head and neck squamous cell carcinoma. The purpose of this study was to investigate the association between lymph node counts from neck dissection, local-regional recurrence, and overall survival.The number of lymph nodes counted from neck dissection in patients treated in 2 NRG Oncology trials (Radiation Therapy Oncology Group [RTOG] 9501 and RTOG 0234) was evaluated for its prognostic impact on overall survival with a multivariate Cox model adjusted for demographic, tumor, and lymph node data and stratified by the postoperative treatment group.Five hundred seventy-two patients were analyzed at a median follow-up of 8 years. Ninety-eight percent of the patients were pathologically N+. The median numbers of lymph nodes recorded on the left and right sides were 24 and 25, respectively. The identification of fewer than 18 nodes was associated with worse overall survival in comparison with 18 or more nodes (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.09-1.74; P=.007). The difference appeared to be driven by local-regional failure (HR, 1.46; 95% CI, 1.02-2.08; P=.04) but not by distant metastases (HR, 1.08; 95% CI, 0.77-1.53; P=.65). When the analysis was limited to NRG Oncology RTOG 0234 patients, adding the p16 status to the model did not affect the HR for dissected nodes, and the effect of nodes did not differ with the p16 status.The removal and identification of 18 or more lymph nodes was associated with improved overall survival and lower rates of local-regional failure, and this should be further evaluated as a measure of quality in neck dissections for mucosal squamous cell carcinoma. Cancer 2016. 2016 American Cancer Society.

Abstract

Definitive assessment of primary site margin status following resection of head and neck cancer is necessary for prognostication, treatment determination and qualification for clinical trials. This retrospective analysis determined how often an independent reviewer can assess primary tumor margin status of head and neck cancer resections based on review of the pathology report, surgical operative report, and first follow-up note alone.We extracted from the electronic medical record pathology reports, operative reports, and follow-up notes from head and neck cancer resections performed at Stanford Hospital. We classified margin status as definitive or not. We labeled any pathology report clearly indicating a positive, negative, or close (<5mm) margin as definitive. For each non-definitive pathology report, we reviewed the operative report and then the first follow-up note in an attempt to clarify margin status. We also looked for associations between non-definitive status and surgeon, year, and primary site.743 unique cases of head and neck cancer resection were extracted. We discarded 255 as non-head and neck cancer cases, or cases that did not involve a definitive resection of a primary tumor site. We could not definitively establish margin status in 20% of resections by independent review of the medical record. There was no correlation between margin determination and surgeon, site, or year of surgery.A substantial fraction (20%) of primary site surgical margins could not be definitively determined via independent EMR review. This could have implications for subsequent patient care decisions and clinical trial options.

Abstract

Definitive assessment of primary site margin status following resection of head and neck cancer is necessary for prognostication, treatment determination and qualification for clinical trials. This retrospective analysis determined how often an independent reviewer can assess primary tumor margin status of head and neck cancer resections based on review of the pathology report, surgical operative report, and first follow-up note alone.We extracted from the electronic medical record pathology reports, operative reports, and follow-up notes from head and neck cancer resections performed at Stanford Hospital. We classified margin status as definitive or not. We labeled any pathology report clearly indicating a positive, negative, or close (<5mm) margin as definitive. For each non-definitive pathology report, we reviewed the operative report and then the first follow-up note in an attempt to clarify margin status. We also looked for associations between non-definitive status and surgeon, year, and primary site.743 unique cases of head and neck cancer resection were extracted. We discarded 255 as non-head and neck cancer cases, or cases that did not involve a definitive resection of a primary tumor site. We could not definitively establish margin status in 20% of resections by independent review of the medical record. There was no correlation between margin determination and surgeon, site, or year of surgery.A substantial fraction (20%) of primary site surgical margins could not be definitively determined via independent EMR review. This could have implications for subsequent patient care decisions and clinical trial options.

Abstract

The purpose of this study was to evaluate a telemedicine model that utilizes an audiovisual teleconference as a preoperative visit.Veterans Health Administration (VHA) patients with head and neck cancer at 2 remote locations were provided access to the Palo Alto Veterans Affairs (PAVA) Health Care System otolaryngology department via the telemedicine protocol: tissue diagnosis and imaging at the patient site; data review at PAVA; and a preoperative teleconference connecting the patient to PAVA. Operative care occurred at PAVA. Follow-up care was provided remotely via teleconference.Fifteen patients were evaluated. Eleven underwent surgery, 4 with high-grade neoplasms (carcinoma). Average time from referral to operation was 28 days (range, 17-36 days) and 72 (range, 31-108 days), respectively, for high-grade and low-grade groups. The average patient was spared 28 hours traveling time and $900/patient was saved on travel-related costs.A telemedicine model enables timely access to surgical care and permits considerable savings among select VHA patients with head and neck cancer. 2016 Wiley Periodicals, Inc. Head Neck 38: 925-929, 2016.

Abstract

Recent changes in head and neck cancer epidemiology have created a need for improved lymph node prognostics. This article compares the prognostic value of the number of positive nodes (pN) with the value of the lymph node ratio (LNR) and American Joint Committee on Cancer (AJCC) N staging in surgical patients.The Surveillance, Epidemiology, and End Results database was used to identify cases of head and neck squamous cell carcinomas from 2004 to 2012. The sample was grouped by the AJCC N stage, LNR, and pN and was analyzed with Kaplan-Meier and multivariate Cox proportional hazards models. The sample was also analyzed by the site of the primary tumor.This study identified 12,437 patients. Kaplan-Meier survival curves showed superior prognostic ability for LNR and pN staging in comparison with AJCC staging. Patients with a pN value > 5 had the worst overall survival (5-year survival rate, 16%). Patients with oropharyngeal tumors had better outcomes for all groupings, and a pN value > 5 for oropharyngeal cancers was associated with decreased survival. Multivariate regressions demonstrated larger hazard ratios (HRs) and a lower Akaike information criterion for the pN model versus the AJCC stage and LNR models. The HRs were 1.78 (95% confidence interval, 1.62-1.95) for a pN value of 1, 2.53 (95% confidence interval, 2.32-2.75) for a pN value of 2 to 5, and 4.64 (95% confidence interval, 4.18-5.14) for a pN value > 5.The pN models demonstrated superior prognostic value in comparison with the LNR and AJCC N staging. Future modifications of the nodal staging system should be based on the pN with a separate system for oropharyngeal cancers. Future trials should consider examining adjuvant treatment escalation in patients with >5 lymph nodes. Cancer 2016;122:1388-1397. 2016 American Cancer Society.

Regional variation in head and neck cancer mortality: Role of patient and hospital characteristicsHEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECKDivi, V., Ma, Y., Rhoads, K. F.2016; 38: E1896-E1902

Abstract

The purpose of this study was to determine whether outcomes in head and neck cancer would vary based on geographic location of patients.A dataset from the California Cancer Registry was linked to publicly available discharge abstracts. Patients were separated into geographic areas based on health service areas (HSAs). Multilevel logistic regression models were constructed to include geographic, patient, and hospital-level characteristics.There was significant variation in 5-year survival hazard ratios (HRs) among the majority of the 14 HSAs in the unadjusted model. After adjusting for patient and hospital characteristics, the differences between regions were not significant except for Orange County (HR = 0.75). Commission on Cancer certification (HR = 0.82; p < .01) and hospital volume (HR = 0.975; p < .01) were each independently associated with differences in survival.Geographic variation in 5-year survival outcomes is seen in head and neck cancer. Patient characteristics and treating hospitals explain much of this variation. 2015 Wiley Periodicals, Inc. Head Neck 38: E1896-E1902, 2016.

Abstract

Oroantral fistula (OAF) is a pathologic, epithelialized communication between the oral cavity and the maxillary sinus. OAF most commonly results from posterior maxillary tooth or molar extraction owing to proximity of the dental roots to the maxillary antrum and the thinness of the adjacent antral floor. It also can arise secondary to implant and orthognathic surgeries, cyst and tumor removal, dental infection, trauma, or as a sequela of radiation therapy. Communications larger than 5mm are less likely to heal spontaneously and can epithelialize, forming an OAF. When locoregional flaps and grafts are not ideal or have failed, but primary OAF closure is mandated, surgical options are unclear. This report describes a novel method for autologous tissue flap coverage from the nasal septum, pedicled off the posterior septal artery, for successful extension to, and closure of, OAFs.

Abstract

Electronic data collection is increasingly used for quality of life (QOL) assessments in the field of oncology. It is important to assess the feasibility of these new data capture technologies.Patients at our institution who were 18years or older with a pathological diagnosis of head and neck cancer were prospectively enrolled. Each patient completed two questionnaires [EORTC-QLQ-C30 and EORTC-QLQ-H&N35] administered on a touch-screen tablet device (iPad) at initial consult, during treatment, at the completion of treatment and at each subsequent follow up visit for one year after treatment.A total of 50 patients were included in this study. Although all patients completed the surveys at the initial consult, 86% of initially enrolled patients completed surveys at the end of radiation treatment, and 48% of initially enrolled patients completed surveys by the fourth follow-up visit. Average time to complete the survey for all patients over all time points was 9.8min (standard deviation 6.1). Age as a continuous variable was significantly associated with time for survey completion (p<0.001), with older age associated with longer survey completion times.QOL assessment using tablet devices in head and neck cancer patients is feasible, but may be more challenging in elderly patients. Patients 70years old may benefit from more assistance with electronic forms and should be allotted more time for completing tablet-based QOL surveys.

Abstract

Transcervical approaches to the upper cervical spine are challenging because several upper anterior neurovascular structures need to be displaced to provide access. Although various techniques have been described, the anterolateral approach is one of the safest and most effective methods available to access the anterior C2-C3 disc space. Despite the approach's efficacy, however, it can cause postoperative complications because of, at least partly, the inter-surgeon differences in the methods by which the larynx and hypopharynx are displaced medially.We present a case report of a patient treated with a modified anterolateral approach to C2-C3. The approach provided excellent visualization while protecting vital structures. The patient recovered without any postoperative dysphagia or other surgical complications.The anterolateral approach to C2-C3 described herein safely protects the contents of the submandibular triangle while providing a wide exposure for direct access to the C2-C3 disc space. 2015 Wiley Periodicals, Inc. Head Neck 37: E115-E119, 2015.

Abstract

Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule.

Abstract

Cancer stem cells possess the qualities of self-renewal, tumorigenesis and the ability to recapitulate a heterogeneous tumor. Our group was the first to isolate head and neck squamous cell carcinoma (HNSCC) stem cells using the cell surface marker CD44. CD44 is a trans-membrane glycoprotein with a multitude of key-functions that regulate cancer cell proliferation and metastasis. The variety of CD44 functions is due to tissue-specific patterns of glycosylation of the extracellular portion, and to the multiple protein isoforms (CD44 variants, CD44v) generated by alternative splicing. This study investigates the expression pattern of CD44 variants in HNSCC. Ten cell lines from the most common HNSCC locations and representative of various clinical outcomes were assayed by quantitative realtime PCR, flow cytometry and immunofluorescence comparatively with normal oral keratinocytes. The CD44 v4 and v6 were exclusively abundant in HNSCC while the isoform v1,2 was expressed in normal oral keratinocytes. Of interest, the highest level of CD44v6 expression was detected in advanced metastatic HNSCC, suggesting a link between CD44v6 expression and HNSCC metastasis, while the highest CD44v4 was detected in a stage IV HNSCC refractory to chemotherapy which developed recurrence. Oral-derived HNSCC expressed the highest CD44v4 and v6, and levels corresponded with staging, showing also an increasing tendency with recurrence and metastasis. CD44v were detected predominantly in smaller cells (a characteristic that has been associated with stem cell properties) or cells with mesenchymal morphology (a characteristic that has been associated with the migratory and invasive potential of epithelial tumor cells), suggesting that CD44v differential expression in HNSCC may be representative of the morphological changes inherent during tumor progression towards a more aggressive potential, and thus contributing to the individual tumor biology. The mechanism of CD44 variant involvement in HNSCC progression and metastasis is under investigation.

Abstract

The long-term outcome of patients with mucoepidermoid carcinoma is poor. Limited availability of cell lines and lack of xenograft models is considered a major barrier to improved mechanistic understanding of this disease and development of effective therapies.To generate and characterize human mucoepidermoid carcinoma cell lines and xenograft models suitable for mechanistic and translational studies.Five human mucoepidermoid carcinoma specimens were available for generation of cell lines. Cell line tumorigenic potential was assessed by transplantation and serial in vivo passaging in immunodeficient mice, and cell line authenticity verified by short tandem repeat (STR) profiling.A unique pair of mucoepidermoid carcinoma cell lines was established from a local recurrence (UM-HMC-3A) and from the metastatic lymph node (UM-HMC-3B) of the same patient, 4years after surgical removal of the primary tumor. These cell lines retained epithelial-like morphology through 100 passages in vitro, contain the Crtc1-Maml2 fusion oncogene (characteristic of mucoepidermoid carcinomas), and express the prototypic target of this fusion (NR4A2). Both cell lines generated xenograft tumors when transplanted into immunodeficient mice. Notably, the xenografts exhibited histological features and Periodic Acid Schiff (PAS) staining patterns that closely resembled those found in human tumors. STR profiling confirmed the origin and authenticity of these cell lines.These data demonstrate the generation and characterization of a pair of tumorigenic salivary mucoepidermoid carcinoma cell lines representative of recurrence and lymph node metastasis. Such models are useful for mechanistic and translational studies that might contribute to the discovery of new therapies for mucoepidermoid carcinoma.

Transoral robotic biopsy of the tongue base: A novel paradigm in the evaluation of unknown primary tumors of the head and neckHEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECKAbuzeid, W. M., Bradford, C. R., Divi, V.2013; 35 (4): E126-E130

Abstract

Squamous cell carcinoma of the head and neck can present as a cervical metastasis from an unknown primary site. The standard diagnostic workup includes panendoscopy and directed biopsies but this will fail to identify a portion of unknown primary tumors.Herein, we present a case report of a male patient with an unknown primary tumor in which the da Vinci surgical robot was used to evaluate the tongue base.Clinical evaluation, imaging, and panendoscopy with directed biopsies failed to detect the primary tumor site. Robot-assisted biopsy of a broad area of the tongue base, incorporating submucosal tissue, identified the primary tumor with minimal postoperative morbidity.Failure to localize an unknown primary tumor often results in widespread irradiation of the upper aerodigestive tract, inducing significant morbidity. Robot-assisted biopsies of the tongue base may identify unknown primaries that would otherwise have been missed through standard directed biopsy techniques.

Abstract

To determine if the various imaging modalities for distant metastasis (DM) diagnosis alters life expectancy in head and neck squamous cell carcinoma (HNSCC).Retrospective.One hundred seventy patients (mean age, 59.1 years; male:female, 135:35) with HNSCC who developed DM were reviewed. The main outcome measures were the method of DM diagnosis and time from DM diagnosis to death while controlling for clinical parameters (age, gender, tobacco status, primary tumor site, initial TNM classification, number and site of DM, administration of palliative chemotherapy).Tumor subsites were: 40 oral cavity, 75 oropharynx, 36 larynx, 10 hypopharynx, one nasopharynx, and eight unknown primary. Of the patients, 16.5% (28/170) had distant metastasis at presentation; the remaining 142 patients were diagnosed with DM at a median of 324 days from diagnosis. Although patients diagnosed with DM by positron-emission tomography (PET) scan were more likely to have multiple DM sites (P = .0001), there were no differences in life expectancy in patients who were diagnosed with or without PET scan (median, 185 vs. 165 days, P = .833). There were no differences in life expectancy based on age, gender, site of primary tumor, or number/site of DM. The use of palliative chemotherapy resulted in a significantly longer life expectancy (median, 285 vs. 70 days; P = .001).Although a PET scan is more likely to diagnose multiple DM sites, there was no difference in life expectancy based on imaging modality. Patients who are symptomatic from their distant metastasis have a worse life expectancy, and palliative chemotherapy was able to increase life expectancy, even in patients who were symptomatic from the distant metastasis.

Abstract

Facial nerve paralysis can occasionally result from the treatment of head and neck cancer. The treatment of paralysis is patient specific, and requires an assessment of the remaining nerve segments, musculature, functional deficits, anticipated recovery, and patient factors. When feasible, reinnervation of the remaining musculature can provide the most natural outcome. However, the complex and topographic nature of facial innervation often prevents complete and meaningful movement. In these instances, a wide variety of procedures can be used to combat the functional and cosmetic sequella of facial paralysis.

Abstract

The authors examined the feasibility and advantages of primary tracheoesophageal puncture (TEP) with intraoperative placement of the voice prosthesis for patients undergoing laryngopharyngectomy requiring free tissue reconstruction and salivary bypass tube placement. Six patients were identified; 4 underwent total laryngopharyngectomy, and 2 underwent total laryngectomy with partial pharyngectomy. All 6 required free tissue reconstruction, and a salivary bypass tube was placed in all cases. All patients had a 20F Indwelling Blom-Singer prosthesis (InHealth Technologies, Carpinteria, California) placed. No complications were noted with intraoperative prosthesis placement. No prostheses were dislodged in the postoperative period. At 6 months, 4 patients available for evaluation had successful voice outcomes, and 3 were disease free. This study demonstrates the effectiveness of voice prosthesis placement at the time of primary TEP associated with free tissue reconstruction of a laryngopharyngeal defect with salivary bypass tube placement.

Abstract

to design in vitro and in vivo models of metastasis to study the behavior of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC).cells were sorted for CD44 expression using flow cytometry. Sorted cells were used in an in vitro invasion assay. For in vivo studies, CSCs and non-CSCs were injected into the tail veins of mice, and lungs were either harvested or imaged to evaluate for lesions.in vitro, CD44(high) cells were more motile but not more invasive than CD44(low) cells. In vivo, 8 of 17 mice injected with CD44(high) cells and 0 of 17 mice injected with CD44(low) cells developed lung lesions. Two of the lesions arose from CSCs from a primary tumor and 6 from CSCs from HNSCC cell lines.in vitro, CSCs do not have an increased ability to invade through basement membrane, but they migrate more efficiently through a porous barrier. In contrast, CSCs efficiently formed lung lesions in vivo, whereas non-CSCs did not give rise to any distant disease. This phenomenon could be due to the enhanced migratory capacity of CSCs, which may be more important than basement membrane degradation in vivo.

Abstract

For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy.Thirty-two patients with advanced laryngeal or hypopharyngeal cancer received 1 cycle of induction chemotherapy, and subsequent treatment was decided based on response.A histologic complete response was achieved in 4 patients and were treated with chemotherapy alone. All 4 patients' cancer relapsed in the neck and required surgery and postoperative radiotherapy (RT). Twenty-five patients were treated with concomitant chemoradiation. Three patients were treated with surgery. Overall survival and disease-specific survival at 3 years were 68% and 78%, respectively.Chemotherapy alone is not feasible for long-term control of regional disease in patients with advanced laryngeal cancer even when they achieve a histologic complete response at the primary site.

Abstract

The purpose of this study was to determine the diagnostic accuracy of using the retromandibular vein as seen on cross-sectional imaging to help differentiate superficial lobe from deep lobe tumors.Of the patients who had parotid neoplasms between January 1997 and July 2002, we were able to identify 44 patients with preoperative imaging studies that were available for evaluation. The films were reviewed by a single head and neck radiologist to determine whether the neoplasms involved the superficial, deep, or both lobes of the parotid gland (total). The lateral margin of the retromandibular vein was used as a marker for the facial nerve, since the nerve is not always visible on CT and MRI scans. The radiologist's findings were then compared with the findings during surgery. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of predicting the location of neoplasms were then calculated.For lesions in the superficial lobe, cross-sectional imaging was able to predict the location of the neoplasm with a sensitivity of 0.91 (95% CI, 0.70-0.98), specificity of 0.86 (95% CI, 0.63-0.96), PPV of 0.88 (95% CI, 0.67-0.97), and NPV of 0.90 (95% CI, 0.67-0.98). For lesions in both lobes (total), cross-sectional imaging was able to predict the location of the neoplasm with a sensitivity of 0.94 (95% CI, 0.68-0.99), specificity of 0.89 (95% CI, 0.71-0.97), PPV of 0.83 (95% CI, 0.58-0.96), and NPV of 0.96 (95% CI, 0.78-0.99).Use of the retromandibular vein as a marker for the facial nerve is a sensitive method for identifying the location of parotid gland neoplasms on cross-sectional imaging. This supports the accuracy of using preoperative imaging to detect the position of parotid neoplasms with respect to the facial nerve.